Ion pumps, cotransport systems and channels are present in animal cell membranes to maintain cellular ionic composition, to transport electrolytes and fluid across epithelia, and to regulate cell volume and maintain osmotic balance. Furthermore, in cornea and lens, epithelial ionic/fluid transport systems are critical for maintaining the transparency of these tissues. Although the functional integrity of the endothelium is essential for corneal transparency, the epithelium may also play a role. Because medical management of physiological function is limited, basic research that may lead to the development of methods to either enhance or limit fluid transport is highly relevant. Likewise, cataract is a prevalent health problem for which there is no medical treatment. Many mechanisms contribute to the maintenance of lens transparency. It is clear that among many unknown factors, osmotic equilibrium, Na/K ATPase activity and normal GSH levels are necessary for lens clarity. The overall aim of this proposal is to further characterize regulatory mechanisms of ion/fluid transport, membrane permeability, and related physiological parameters relevant to the understanding of corneal and lens cell function. In addition, some experiments will use the ciliary body epithelium, a tissue studied in this laboratory in the past: Electrophysiological, radiolabeled tracer and fluorometric techniques will be used in three specific aims: l) Characterization of water permeability (P-f and P-dw) and its regulation in corneal, lens and ciliary body epithelia; 2) Characterization of the distribution of ionic currents and conductances around the lens surface; and 3) Characterization of Na-K-2Cl cotransport activity in the lens. These aims will extend recent original findings of this laboratory. From the accomplishment of these aims, models of lens and corneal physiological function will be provided.